Altering hydrodynamic variables influences PGI2 production by isolated lungs and endothelial cells

Grondelle, Albertus van; Worthen, G. Scott; Ellis, Dorette Z.; Mathias, Melvin M.; Murphy, Rachel; Strife, Robert J.; Reeves, J. T.; Voelkel, Norbert F.

doi:10.1152/jappl.1984.57.2.388

Cited by 78 publications

(16 citation statements)

References 13 publications

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“…A possible explanation for this effect of cyclooxygenase inhibition is that in control isolated lungs the manipulation involved in the preparation caused an increase in PG release resulting in greater modulation of HPV than seen in intact animals. Indirect support for this idea includes the observation that rapid ventilatory rates (32) and rapid alteration in vascular pressures or flow rates (33) caused an increase in PGIz production. That isolated lungs may produce more dilator PG is also supported by the findings that meclofenamate did not accentuate HPV in intact piglets between 5 and 88 d of life (4) and in intact 2-to 3-wk-old lambs, indomethacin had only a transient effect on hypoxic vasoreactivity (34).…”

Section: Discussionmentioning

confidence: 99%

Developmental Effects of Hypoxia and Indomethacin on Distribution of Vascular Resistances in Lamb Lungs

1989

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ABSTRACT. The influence of postnatal age on the distribution of vascular resistances was studied in in situ, isolated, blood perfused lungs of lambs aged 6-12 h, 2-4 d, 2 wk, and 1 mo. The pressure gradients across the upstream, downstream, and compliant middle segments were determined by an inflow-outflow occlusion technique during mild hyperoxia (FI02 = 0.28) and severe hypoxia (FI02 = 0.04) under control and indomethacin-treated conditions. The greatest response to hypoxia was seen in the middle segment. A lesser, but significant response was also seen in the upstream segment. Indomethacin accentuated the hypoxic response of the total circuit and the middle segment at all ages, and the upstream segment in the two younger age groups. An age-dependent increase in total hypoxic reactivity was seen in control lungs, but not in indomethacin-treated lungs. When the pressure gradient across the middle segment alone was considered, an age-dependent increase in hypoxic reactivity was seen in controls and a decrease was seen in indomethacin-treated lungs. In contrast there were no age-dependent changes in the hypoxic responses of the upstream or downstream segments. These data suggest that the predominant site of hypoxic pulmonary vasoconstriction and dilator prostaglandin activity lies within the middle gradient in newborn lamb lungs. Purthermore, the age-dependent changes in the hypoxic response of the middle gradient appear to be altered by the modulating influence of dilator prostaglandins. (Pediatr Res 26:325-329,1989) Abbreviations HPV, hypoxic pulmonary vasoconstriction PVR, pulmonary vascular resistance PG, prostaglandin Paw, tracheal pressure Ppa, Pulmonary artery pressure Pla, left atrial pressure yIOz, fractional inspired oxygen Q, constant flow LSD, least significant different test APm, middle segment gradient Apt, total pressure gradient APa, upstream gradient APv, downstream gradient It has long been established that normoxic PVR decreases rapidly after birth (1-3). In contrast, although some studies have shown that the vigor of HPV also decreases (3-5), others have indicated that HPV increases with age (6-1 1). In piglets the increase in hypoxic reactivity was positively correlated with the peripheral extension of arteriolar muscularization (9, 10) suggesting that arterioles might be the site of HPV. However, other newborn studies suggested that veins, not arterioles are the site of HPV (12)(13)(14). Moreover, in a previous study we found that dilator PC appeared to modulate HPV more in isolated lungs of 2-to 4-d than 2-wk-old lambs, suggesting that factors other than vascular muscularization may also influence the age-dependent changes in HPV (8).In this study we examined the effects of hypoxia (FI02 = 0.04) on the distribution of pulmonary vascular resistances in isolated lamb lungs under control and indomethacin-treated conditions at four ages during the 1 st mo of life. We used an inflow-outflow occlusion technique to partition the pulmonary vascular circuit into relatively noncompliant upstream ...

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Section: Discussionmentioning

confidence: 99%

Developmental Effects of Hypoxia and Indomethacin on Distribution of Vascular Resistances in Lamb Lungs

1989

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“…For example, changes in blood flow or shear stress can stimulate prostacyclin (7,8) or NO release (9,10). NO or a closely related molecule enzymatically derived from L-arginine (9, 10) is a potent pulmonary vasodilator and regulates pulmonary vascular tone in some species ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Changes in pulmonary vascular tone during exercise. Effects of nitric oxide (NO) synthase inhibition, L-arginine infusion, and NO inhalation.

Koizumi¹,

Gupta²,

Banerjee³

et al. 1994

J. Clin. Invest.

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Nitric oxide (NO) is a potent endogenous vasodilator. Its role in the normal and stressed pulmonary circulation is unclear. To better understand the importance of endogenous NO in normal physiological responses, we studied the effects of altered NO availability on the change in pulmonary vascular tone that accompanies exercise. In paired studies we measured blood flow and pressures in the pulmonary circulation at rest and during treadmill exercise at a speed of 4 mph with and without (a) NW-nitro-L-arginine, 20 mg/kg intravenously, a selective inhibitor of NO synthase; (b) L-arginine, 200 mg/kg intravenously, substrate for NO synthase; (c) combination of the inhibitor and substrate; and (d) inhalation of NO > 30 ppm, to determine if endogenous release of NO elicits maximal vasodilation. In addition, we sought to determine the site of NO effect in the pulmonary circulation by preconstriction with either U-44619 or hypoxia (fraction of inspired 02 = 0.12) using a distal wedged pulmonary catheter technique. NO synthase inhibition raised pulmonary vascular tone equally at rest and exercise. L-Arginine reversed the effects of NO synthase inhibition but had no independent effect. NO inhalation did not reduce pulmonary vascular tone at rest or enhance the usual reduction in pulmonary vascular resistance with exercise. The effect of NO synthase inhibition was in pulmonary vessels upstream from small veins, suggesting that endogenous NO dilates primarily small arteries and veins at rest. We conclude that, in sheep, endogenous NO has a basal vasodilator function that persists during, but is not enhanced by, exercise. (J. Clin. Invest. 1994Invest. . 94:2275Invest. -2282

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“…in species other than dogs, such as rabbits (Armstrong et al, 1981). Moreover, PG12 is released during pulmonary oedema (Van Grondelle et al, 1984), and vagal reflexes evoked by this condition in the absence of congestion result largely from stimulation of lung C-fibres (Roberts et al, 1986). PG12 is also the major arachidonate metabolite via the cyclo-oxygenase pathway produced during vasoconstriction by the rat isolated lung (Voelkel et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Prostacyclin activates tachykinin release from capsaicin‐sensitive afferents in guinea‐pig bronchi through a ruthenium red‐sensitive pathway

Mapp

Fabbri

Boniotti

et al. 1991

British J Pharmacology

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1 We have investigated the ability of prostacyclin (PGO2) to contract guinea-pig isolated bronchi and the possible involvement of capsaicin-sensitive primary afferents in the response to PG12 . 2 PGO2 (0.1-100pUM) produced concentration-dependent contractions of the guinea-pig isolated bronchi. In vitro capsaicin desensitization (10pM for 30min followed by washing) significantly reduced the PG12-induced contraction at all concentrations tested. A capsaicin-resistant component of contraction (40-60% of the overall response) was also evident. 3 Ruthenium red (3pM), an inorganic dye which acts as a selective functional antagonist of capsaicin, significantly decreased PG12-induced contractions, without affecting the response to substance P, neurokinin A or acetylcholine.4 MEN 10, 207, (Tyr5, D-Trp6'8'9, Arg10)-neurokinin A (4-10) (3pM), a selective antagonist of NK2-tachykinin receptors, significantly decreased PG12-induced contractions and neurokinin A-induced contractions, without affecting the response to acetylcholine. 5 The effect of ruthenium red and MEN 10,207 on the one hand, and that of ruthenium red and capsaicin on the other was non additive. 6 These results indicate that PGI2-induced contraction of the guinea-pig isolated bronchi involves two distinct mechanisms, one of which involves transmitter (tachykinins) release from peripheral endings of capsaicin-sensitive primary afferents. In as much as PG12-activation of primary afferents is sensitive to ruthenium red, we suggest that PGO2 shares a common mechanism of tachykinin release with that activated by capsaicin.

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Altering hydrodynamic variables influences PGI2 production by isolated lungs and endothelial cells

Cited by 78 publications

References 13 publications

Developmental Effects of Hypoxia and Indomethacin on Distribution of Vascular Resistances in Lamb Lungs

Developmental Effects of Hypoxia and Indomethacin on Distribution of Vascular Resistances in Lamb Lungs

Changes in pulmonary vascular tone during exercise. Effects of nitric oxide (NO) synthase inhibition, L-arginine infusion, and NO inhalation.

Prostacyclin activates tachykinin release from capsaicin‐sensitive afferents in guinea‐pig bronchi through a ruthenium red‐sensitive pathway

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